Generating a self-organizing kidney from pluripotent cells

Melissa H. Little, Minoru Takasato

Recent studies on the directed differentiation of human pluripotent stem cells report tissue self-organization in vitro such that multiple component cell types arise in concert and arrange with respect to each, thereby recapitulating the morphogenetic events typical for that organ. Such self-organization has generated pituitary, optic cup, liver, brain, intestine, stomach and now kidney. Here, we will describe the cell types present within the self-organizing kidney, how these signal to each other to form a kidney organoid and the potential applications of kidney organoids. Protocols for the directed differentiation of human pluripotent cells focus on recapitulating the developmental steps required during embryogenesis. In the case of the kidney, this has involved mesodermal differentiation through posterior primitive streak and intermediate mesoderm. Recent studies have observed the simultaneous formation of both ureteric epithelium and nephron progenitors in vitro. These component cell types signal to each other to initiate nephron formation as would occur during development. The generation of kidney organoids is a major advance in nephrology. Such organoids may be useful for disease modelling and drug screening. Ultimately, our capacity to generate organoids may extend to the development of tissues for transplantation.